It is proposed to investigate the effect of a variety of physiological states on the activity, synthesis and decay of HMG-CoA reductase in liver and intestinal mucosa, of rats and mice. This enzyme plays a major role in controlling the rate of synthesis of cholesterol. These parameters will be evaluated with the aid of an antibody to the enzyme which is monospecific. The antibody also cross-reacts with the enzyme from mice. It is also proposed to study by a variety of physical techniques, the variation in the structure of the enzyme which leads to wide changes in the specific-activity and properties of the enzyme prepared by different investigators. This will include the nature of the inhibited enzyme during the early phases of cholesterol feeding. The role of certain cholesterol derivatives which are known to be inhibitors of HMG-CoA reductase activity will also be investigated.